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C
CARISOPRODOL Tablets, USP for Oral use IV
Initial U.S. Approval: 1959
------------------------------------ INDICATIONS AND USAGE -------------------------------------CARISOPRODOL Tablets, USP is indicated for the relief of discomfort associated with
acute, painful musculoskeletal conditions in adults. (1)
Limitations of Use:
• Should only be used for acute treatment periods up to two or three weeks (1)
--------------------------------- DOSAGE AND ADMINISTRATION --------------------------------Recommended dose is 250 mg to 350 mg three times a day and at bedtime. (2)
--------------------------------DOSAGE FORMS AND STRENGTHS-------------------------------Tablets: 350 mg (3)
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Sedation
5.2 Abuse, Dependence, and Withdrawal
5.3 Seizures
6 ADVERSE REACTIONS
6.1 Clinical Studies Experience
6.2 Post-marketing Experience
7 DRUG INTERACTIONS
7.1 CNS Depressants
7.2 CYP2C19 Inhibitors and Inducers
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy: Pregnancy Category C.
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
Carisoprodol tablets, USP is indicated for the relief of discomfort associated with acute,
painful musculoskeletal conditions in adults.
Carisoprodol tablets, USP should only be used for short periods (up to two or three weeks)
because adequate evidence of effectiveness for more prolonged use has not been
established and because acute, painful musculoskeletal conditions are generally of short
duration [see Dosage and Administration (2)].
2
DOSAGE AND ADMINISTRATION
The recommended dose of carisoprodol tablets, USP is 250 mg to 350 mg three times a day
and at bedtime. The recommended maximum duration of carisoprodol tablets, USP use is
up to two or three weeks.
3
DOSAGE FORMS AND STRENGTHS
350 mg Tablets: round, convex, white tablets, debossed with SG 109 on one side
4
CONTRAINDICATIONS
Carisoprodol tablets, USP is contraindicated in patients with a history of acute intermittent
porphyria or a hypersensitivity reaction to a carbamate such as meprobamate.
5
WARNINGS AND PRECAUTIONS
5.1
Sedation
Carisoprodol has sedative properties (in the low back pain trials, 13% to 17% of patients
who received carisoprodol experienced sedation compared to 6% of patients who received
placebo) [see ADVERSE REACTIONS (6.1)] and may impair the mental and/or physical
abilities required for the performance of potentially hazardous tasks such as driving a motor
vehicle or operating machinery. There have been post-marketing reports of motor vehicle
accidents associated with the use of carisoprodol.
Since the sedative effects of carisoprodol and other CNS depressants (e.g., alcohol,
benzodiazepines, opioids, tricyclic antidepressants) may be additive, appropriate caution
should be exercised with patients who take more than one of these CNS depressants
simultaneously.
5.2
Abuse, Dependence, and Withdrawal
Carisoprodol, the active ingredient in carisoprodol tablets, USP, has been subject to abuse,
dependence, and withdrawal, misuse and criminal diversion. [see Drug Abuse and
Dependence (9.1, 9.2, 9.3)]. Abuse of carisoprodol tablets, USP poses a risk of overdosage
which may lead to death, CNS and respiratory depression, hypotension, seizures, and other
disorders [see Overdosage (10)].
Post-marketing experience cases of carisoprodol abuse and dependence have been
reported in patients with prolonged use and a history of drug abuse. Although most of these
patients took other drugs of abuse, some patients solely abused carisoprodol. Withdrawal
symptoms have been reported following abrupt cessation of carisoprodol after prolonged
use. Reported withdrawal symptoms included insomnia, vomiting, abdominal cramps,
headache, tremors, muscle twitching, ataxia, hallucinations, and psychosis. One of
carisoprodol’s metabolites, meprobamate (a controlled substance), may also cause
dependence [see Clinical Pharmacology (12.3)].
To reduce the risk of carisoprodol tablets, USP abuse assess the risk of abuse prior to
prescribing. After prescribing, limit the length of treatment to three weeks for the relief of
acute musculoskeletal discomfort, keep careful prescription records, monitor for signs of
abuse and overdose, and educate patients and their families about abuse and on proper
storage and disposal.
5.3
Seizures
There have been post-marketing reports of seizures in patients who received carisoprodol.
Most of these cases have occurred in the setting of multiple drug overdoses (including
drugs of abuse, illegal drugs, and alcohol) [see Overdosage (10)].
6
ADVERSE REACTIONS
--------------------------------------CONTRAINDICATIONS-----------------------------------------Acute intermittent porphyria (4)
• Hypersensitivity reactions to a carbamate such as meprobamate (4)
--------------------------------- WARNINGS AND PRECAUTIONS---------------------------------• Due to sedative properties, may impair ability to perform hazardous tasks such as driving
or operating machinery (5.1)
• Additive sedative effects when used with other CNS depressants including alcohol (5.1)
• Cases of abuse, dependence, and withdrawal (5.2, 9.2, 9.3)
• Seizures (5.3)
--------------------------------------ADVERSE REACTIONS----------------------------------------Most common adverse reactions (incidence > 2%) are drowsiness, dizziness, and
headache (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Carlsbad Tech at 1(855) 397-9777
or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
--------------------------------------DRUG INTERACTIONS-----------------------------------------CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) additive sedative effects (5.1, 7.1)
See 17 for PATIENT COUNSELING INFORMATION
Rev. 11/15
8.7 Hepatic Impairment
8.8 Patients with Reduced CYP2C19 Activity
DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
9.2 Abuse
9.3 Dependence
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Sedation
17.2 Avoidance of Alcohol and Other CNS Depressants
17.3 Carisoprodol Should Only Be Used for Short-Term Treatment
9
*Sections or subsections omitted from the full prescribing information are not listed
6.1
Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction
rates observed in clinical studies of a drug cannot be directly compared to rates in the
clinical studies of another drug and may not reflect rates observed in practice.
The data described below are based on 1387 patients pooled from two double blind,
randomized, multicenter, placebo controlled, one-week trials in adult patients with acute,
mechanical, lower back pain [see Clinical Studies (14)]. In these studies, patients were
treated with 250 mg of carisoprodol, 350 mg of carisoprodol, or placebo three times a day
and at bedtime for seven days. The mean age was about 41 years old with 54% females and
46% males and 74% Caucasian, 16% Black, 9% Asian, and 2% other.
There were no deaths and there were no serious adverse reactions in these two trials. In
these two studies, 2.7%, 2%, and 5.4%, of patients treated with placebo, 250 mg of
carisoprodol, and 350 mg of carisoprodol, respectively, discontinued due to adverse
events; and 0.5%, 0.5%, and 1.8% of patients treated with placebo, 250 mg of
carisoprodol, and 350 mg of carisoprodol, respectively, discontinued due to central
nervous system adverse reactions.
Table 1 displays adverse reactions reported with frequencies greater than 2% and more
frequently than placebo in patients treated with carisoprodol in the two trials described
above.
Adverse Reaction
Drowsiness
Dizziness
Headache
Table 1. Patients with Adverse Reactions in Controlled Studies
Placebo
Carisoprodol 250 mg
Carisoprodol 350 mg
(n=560)
(n=548)
(n=279)
n (%)
n (%)
n (%)
31 (6)
73 (13)
47 (17)
11 (2)
43 (8)
19 (7)
11 (2)
26 (5)
9 (3)
6.2
Post-marketing Experience
The following events have been reported during postapproval use of carisoprodol. Because
these reactions are reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal relationship to drug
exposure.
Cardiovascular: Tachycardia, postural hypotension, and facial flushing [see Overdosage
(10)].
Central Nervous System: Drowsiness, dizziness, vertigo, ataxia, tremor, agitation,
irritability, headache, depressive reactions, syncope, insomnia, and seizures [see
Overdosage (10)].
Gastrointestinal: Nausea, vomiting, and epigastric discomfort.
Hematologic: Leukopenia, pancytopenia
7
DRUG INTERACTIONS
7.1
CNS Depressants
The sedative effects of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive. Therefore, caution should be
exercised with patients who take more than one of these CNS depressants simultaneously.
Concomitant use of carisoprodol and meprobamate, a metabolite of carisoprodol, is not
recommended [see Warnings and Precautions (5.1)].
7.2
CYP2C19 Inhibitors and Inducers
Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate [see Clinical
Pharmacology (12.3)]. Co-administration of CYP2C19 inhibitors, such as omeprazole or
fluvoxamine, with carisoprodol could result in increased exposure of carisoprodol and
decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as
rifampin or St. John’s Wort, with carisoprodol could result in decreased exposure of
carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed an
induction effect on CYP2C19. The full pharmacological impact of these potential alterations
1321 Pack Insert for Carisoprodol Tablets, USP 350 mg (Sciegen - Carlsbad) 450-11-15.indd 1
Carisoprodol
Tablets, USP
RxOnly
450-11-15
CARISOPRODOL Tablets, USP
Rx Only
of exposures in terms of either efficacy or safety of carisoprodol is unknown.
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy: Pregnancy Category C.
There are no data on the use of carisoprodol during human pregnancy. Animal studies
indicate that carisoprodol crosses the placenta and results in adverse effects on fetal
growth and postnatal survival. The primary metabolite of carisoprodol, meprobamate, is an
approved anxiolytic. Retrospective, post-marketing studies do not show a consistent
association between maternal use of meprobamate and an increased risk for particular
congenital malformations.
Teratogenic effects: Animal studies have not adequately evaluated the teratogenic effects of
carisoprodol. There was no increase in the incidence of congenital malformations noted in
reproductive studies in rats, rabbits, and mice treated with meprobamate. Retrospective,
post-marketing studies of meprobamate during human pregnancy were equivocal for
demonstrating an increased risk of congenital malformations following first trimester
exposure. Across studies that indicated an increased risk, the types of malformations were
inconsistent.
Nonteratogenic effects: In animal studies, carisoprodol reduced fetal weights, postnatal
weight gain, and postnatal survival at maternal doses equivalent to 1 to 1.5 times the
human dose (based on a body surface area comparison). Rats exposed to meprobamate
in-utero showed behavioral alterations that persisted into adulthood. For children exposed
to meprobamate in-utero, one study found no adverse effects on mental or motor
development or IQ scores. Carisoprodol should be used during pregnancy only if the
potential benefit justifies the risk to the fetus.
8.2
Labor and Delivery
There is no information about the effects of carisoprodol on the mother and the fetus during
labor and delivery.
8.3
Nursing Mothers
Very limited data in humans show that carisoprodol is present in breast milk and may reach
concentrations two to four times the maternal plasma concentrations. In one case report, a
breast-fed infant received about 4% to 6% of the maternal daily dose through breast milk
and experienced no adverse effects. However, milk production was inadequate and the baby
was supplemented with formula. In lactation studies in mice, female pup survival and pup
weight at weaning were decreased. This information suggests that maternal use of
carisoprodol may lead to reduced or less effective infant feeding (due to sedation) and/or
decreased milk production. Caution should be exercised when carisoprodol is administered
to a nursing woman.
8.4
Pediatric Use
The efficacy, safety, and pharmacokinetics of carisoprodol in pediatric patients less than 16
years of age have not been established.
8.5
Geriatric Use
The efficacy, safety, and pharmacokinetics of carisoprodol in patients over 65 years old
have not been established.
8.6
Renal Impairment
The safety and pharmacokinetics of carisoprodol in patients with renal impairment have not
been evaluated. Since carisoprodol is excreted by the kidney, caution should be exercised if
carisoprodol is administered to patients with impaired renal function. Carisoprodol is
dialyzable by hemodialysis and peritoneal dialysis.
8.7
Hepatic Impairment
The safety and pharmacokinetics of carisoprodol in patients with hepatic impairment have
not been evaluated. Since carisoprodol is metabolized in the liver, caution should be
exercised if carisoprodol is administered to patients with impaired hepatic function.
8.8
Patients with Reduced CYP2C19 Activity
Patients with reduced CYP2C19 activity have higher exposure to carisoprodol. Therefore,
caution should be exercised in administration of carisoprodol to these patients [see Clinical
Pharmacology (12.3)].
9
DRUG ABUSE AND DEPENDENCE
9.1
Controlled Substance
Carisoprodol tablets, USP contains carisoprodol, USP a Schedule IV controlled substance.
Carisoprodol has been subject to abuse, misuse, and criminal diversion for nontherapeutic
use [see Warnings and Precautions (5.2)]
9.2
Abuse
Abuse of carisoprodol poses a risk of overdosage which may lead to death, CNS and
respiratory depression, hypotension, seizures and other disorders [see Warnings and
Precautions (5.2) and Overdosage (10)]. Patients at high risk of carisoprodol abuse may
include those with prolonged use of carisoprodol, with a history of drug abuse, or those
who use carisoprodol in combination with other abused drugs.
Prescription drug abuse is the intentional non-therapeutic use of a drug, even once, for its
rewarding psychological effects. Drug addiction, which develops after repeated drug abuse,
is characterized by a strong desire to take a drug despite harmful consequences, difficulty
in controlling its use, giving a higher priority to drug use than to obligations, increased
tolerance, and sometimes physical withdrawal. Drug abuse and drug addiction are separate
and distinct from physical dependence and tolerance (for example, abuse or addiction may
not be accompanied by tolerance or physical dependence) [see Drug Abuse and
Dependence (9.3)].
9.3
Dependence
Tolerance is when a patient’s reaction to a specific dosage and concentration is
progressively reduced in the absence of disease progression, requiring an increase in the
dosage to maintain the same. Physical dependence is characterized by withdrawal
symptoms after abrupt discontinuation or a significant dose reduction of a drug. Both
tolerance and physical dependence have been reported with the prolonged use of
carisoprodol. Reported withdrawal symptoms with carisoprodol include insomnia,
vomiting, abdominal cramps, headache, tremors, muscle twitching, anxiety, ataxia,
hallucinations, and psychosis. Instruct patients taking large doses of carisoprodol or those
taking the drug for a prolonged time to not abruptly stop carisoprodol [see Warnings and
Precautions (5.2)].
10
OVERDOSAGE
Overdosage of carisoprodol commonly produces CNS depression. Death, coma,
respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions,
nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or
headache have been reported with carisoprodol overdosage. Serotonin syndrome has been
reported with carisoprodol intoxication. Many of the carisoprodol overdoses have occurred
in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and
alcohol). The effects of an overdose of carisoprodol and other CNS depressants (e.g.,
alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one
of the drugs has been taken in the recommended dosage. Fatal accidental and
non-accidental overdoses of carisoprodol have been reported alone or in combination with
11/3/15 5:16 PM
CNS depressants.
Treatment of Overdosage: Basic life support measures should be instituted as dictated by
the clinical presentation of the carisoprodol overdose. Vomiting should not be induced
because of the risk of CNS and respiratory depression, and subsequent aspiration.
Circulatory support should be administered with volume infusion and vasopressor agents
if needed. Seizures should be treated with intravenous benzodiazepines and the
reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS
depression, airway protective reflexes may be compromised and tracheal intubation should
be considered for airway protection and respiratory support.
For decontamination in cases of severe toxicity, activated charcoal should be considered in
a hospital setting in patients with large overdoses who present early and are not
demonstrating CNS depression and can protect their airway.
For more information on the management of an overdose of carisoprodol, contact a Poison
Control Center.
11
DESCRIPTION
Carisoprodol tablets, USP are available as 350 mg round, white tablets. Carisoprodol USP
is a white, crystalline powder, having a mild, characteristic odor. It is very slightly soluble in
water; freely soluble in alcohol, in chloroform, and in acetone; and its solubility is practically
independent of pH. Carisoprodol is present as a racemic mixture. Chemically, carisoprodol
is N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate and the molecular formula
is C12H24N2O4, with a molecular weight of 260.33. The structural formula is:
Other ingredients in the carisoprodol tablets USP, 350 mg include microcrystalline
cellulose, lactose monohydrate, pregelatinized starch (botanical source: maize),
croscarmellose sodium, povidone, silicon dioxide and magnesium stearate.
12
CLINICAL PHARMACOLOGY
12.1
Mechanism of Action
The mechanism of action of carisoprodol in relieving discomfort associated with acute
painful musculoskeletal conditions has not been clearly identified.
In animal studies, muscle relaxation induced by carisoprodol is associated with altered
interneuronal activity in the spinal cord and in the descending reticular formation of the
brain.
12.2
Pharmacodynamics
Carisoprodol is a centrally acting skeletal muscle relaxant that does not directly relax
skeletal muscles.
A metabolite of carisoprodol, meprobamate, has anxiolytic and sedative properties. The
degree to which these properties of meprobamate contribute to the safety and efficacy of
carisoprodol is unknown.
12.3
Pharmacokinetics
The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a
crossover study of 24 healthy subjects (12 male and 12 female) who received single doses
of 250 mg and 350 mg carisoprodol (see Table 2). The exposure of carisoprodol and
meprobamate was dose proportional between the 250 mg and 350 mg doses. The Cmax of
meprobamate was 2.5 ± 0.5 mcg/mL (mean ± SD) after administration of a single 350 mg
dose of carisoprodol tablets, which is approximately 30% of the Cmax of meprobamate
(approximately 8 mcg/mL) after administration of a single 400 mg dose of meprobamate.
Table 2. Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean ± SD, n=24)
250 mg carisoprodol
350 mg carisoprodol
Carisoprodol
Cmax (mcg/mL)
1.2 ± 0.5
1.8 ± 1.0
AUCinf (mcg*hr/mL)
4.5 ± 3.1
7.0 ± 5.0
Tmax (hr)
1.5 ± 0.8
1.7 ± 0.8
T1/2 (hr)
1.7 ± 0.5
2.0 ± 0.5
Meprobamate
Cmax (mcg/mL)
1.8 ± 0.3
2.5 ± 0.5
AUCinf (mcg*hr/mL)
Tmax (hr)
T1/2 (hr)
32 ± 6.2
3.6 ± 1.7
9.7 ± 1.7
46 ± 9.0
4.5 ± 1.9
9.6 ± 1.5
Absorption: Absolute bioavailability of carisoprodol has not been determined. The mean
time to peak plasma concentrations (Tmax) of carisoprodol was approximately 1.5 to 2
hours. Co-administration of a high-fat meal with carisoprodol (350 mg tablet) had no effect
on the pharmacokinetics of carisoprodol. Therefore, carisoprodol may be administered with
or without food.
Metabolism: The major pathway of carisoprodol metabolism is via the liver by cytochrome
enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see
Patients with Reduced CYP2C19 Activity below).
Elimination: Carisoprodol is eliminated by both renal and non-renal routes with a terminal
elimination half-life of approximately 2 hours. The half-life of meprobamate is
approximately 10 hours.
Gender: Exposure of carisoprodol is higher in female than in male subjects (approximately
30% to 50% on a weight adjusted basis). Overall exposure of meprobamate is comparable
between female and male subjects.
Patients with Reduced CYP2C19 Activity: Carisoprodol should be used with caution in
patients with reduced CYP2C19 activity. Published studies indicate that patients who are
poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and
concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19
metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is
approximately 3% to 5% and in Asians is approximately 15% to 20%.
13
NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long term studies in animals have not been performed to evaluate the carcinogenic
potential of carisoprodol.
Carisoprodol was not formally evaluated for genotoxicity. In published studies,
carisoprodol was mutagenic in the in vitro mouse lymphoma cell assay in the absence of
metabolizing enzymes, but was not mutagenic in the presence of metabolizing enzymes.
Carisoprodol was clastogenic in the in vitro chromosomal aberration assay using Chinese
hamster ovary cells with or without the presence of metabolizing enzymes. Other types of
genotoxic tests resulted in negative findings. Carisoprodol was not mutagenic in the Ames
reverse mutation assay using S.typhimurium strains with or without metabolizing enzymes,
and was not clastogenic in an in vivo mouse micronucleus assay of circulating blood cells.
Carisoprodol was not formally evaluated for effects on fertility. Published reproductive
studies of carisoprodol in mice found no alteration in fertility although an alteration in
reproductive cycles characterized by a greater time spent in estrus was observed at a
carisoprodol dose of 1200 mg/kg/day. In a 13-week toxicology study that did not determine
fertility, mouse testes weight and sperm motility were reduced at a dose of 1200 mg/kg/day.
In both studies, the no effect level was 750 mg/kg/day, corresponding to approximately 2.6
times the human equivalent dosage of 350 mg four times a day, based on a body surface
area comparison.
The significance of these findings for human fertility is not known.
14
CLINICAL STUDIES
The safety and efficacy of carisoprodol for the relief of acute, idiopathic mechanical low
back pain was evaluated in two, 7-day, double blind, randomized, multicenter, placebo
controlled, U.S. trials (Studies 1 and 2). Patients had to be 18 to 65 years old and had to
have acute back pain (≤ 3 days of duration) to be included in the trials. Patients with chronic
back pain; at increased risk for vertebral fracture (e.g., history of osteoporosis); with a
history of spinal pathology (e.g., herniated nucleus pulposis, spondylolisthesis or spinal
stenosis); with inflammatory back pain, or with evidence of a neurologic deficit were
excluded from participation. Concomitant use of analgesics (e.g., acetaminophen, NSAIDs,
tramadol, opioid agonists), other muscle relaxants, botulinum toxin, sedatives (e.g.,
barbiturates, benzodiazepines, promethazine hydrochloride), and anti-epileptic drugs was
prohibited.
In Study 1, patients were randomized to one of three treatment groups (i.e., carisoprodol
250 mg, carisoprodol 350 mg, or placebo) and in Study 2 patients were randomized to two
treatment groups (i.e., carisoprodol 250 mg or placebo). In both studies, patients received
study medication three times a day and at bedtime for seven days.
The primary endpoints were the relief from starting backache and the global impression of
change, as reported by patients, on Study Day 3. Both endpoints were scored on a 5-point
rating scale from 0 (worst outcome) to 4 (best outcome) in both studies. The primary
statistical comparison was between the carisoprodol 250 mg and placebo groups in both
studies.
The proportion of patients who used concomitant acetaminophen, NSAIDs, tramadol,
opioid agonists, other muscle relaxants, and benzodiazepines was similar in the treatment
groups.
The results for the primary efficacy evaluations in the acute, low back pain studies are
presented in Table 3.
Distributed by:
Carlsbad Tech
5928 Farnsworth Court
Carlsbad, CA 92008
Manufactured by:
ScieGen Pharmaceuticals, Inc.
Hauppauge, NY 11788 USA
Rev. 11/15
a
Study
1
2
Table 3. Results of the Primary Efficacy Endpoints in Studies 1 and 2
Parameter
Placebo carisoprodol
250 mg
Number of Patients
n=269
n=264
b
Relief from Starting Backache, Mean (SE)
1.4 (0.1) 1.8 (0.1)
Difference between carisoprodol and Placebo, Mean
0.4
b
(SE) (95% CI)
(0.2, 0.5)
b
Global Impression of Change, Mean (SE)
1.9 (0.1) 2.2 (0.1)
Difference between carisoprodol and Placebo, Mean
0.2
b
(SE) (95% CI)
(0.1, 0.4)
Number of Patients
b
Relief from Starting Backache, Mean (SE)
Difference between carisoprodol and Placebo, Mean
b
(SE) (95% CI)
b
Global Impression of Change, Mean (SE)
Difference between carisoprodol and Placebo, Mean
b
(SE) (95% CI)
n=278
1.1 (0.1)
1.7 (0.1)
carisoprodol
350 mg
n=273
1.8 (0.1)
0.4
(0.2, 0.6)
2.2 (0.1)
0.3
(0.1, 0.4)
n=269
1.8 (0.1)
0.7
(0.5, 0.9)
2.2 (0.1)
0.5
(0.4, 0.7)
a The primary efficacy endpoints (Relief from Starting Backache and Global Impression of
Change) were assessed by the patients on Study Day 3. These endpoints were scored on a
5-point rating scale from 0 (worst outcome) to 4 (best outcome).
b Mean is the least squared mean and SE is the standard error of the mean. The ANOVA model
was used for the primary statistical comparison between the carisoprodol 250 mg and placebo
groups.
Patients treated with carisoprodol experienced improvement in function as measured by
the Roland-Morris Disability Questionnaire (RMDQ) score on Days 3 and 7.
16
HOW SUPPLIED/STORAGE AND HANDLING
Carisoprodol Tablets, USP 350 mg: round, convex, white tablets, debossed with SG 109
on one side; available in bottles of 100 (NDC 61442-450-01), available in bottles of 500 (NDC
61442-450-05), available in bottles of 1000 (NDC 61442-450-10).
Storage:
Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature].
17
PATIENT COUNSELING INFORMATION
Patients should be advised to contact their physician if they experience any adverse
reactions to carisoprodol.
17.1
Sedation
Patients should be advised that carisoprodol may cause drowsiness and/or dizziness, and
has been associated with motor vehicle accidents. Patients should be advised to avoid
taking carisoprodol before engaging in potentially hazardous activities such as driving a
motor vehicle or operating machinery [see Warnings and Precautions (5.1)].
17.2
Avoidance of Alcohol and Other CNS Depressants
Patients should be advised to avoid alcoholic beverages while taking carisoprodol and to
check with their doctor before taking other CNS depressants such as benzodiazepines,
opioids, tricyclic antidepressants, sedating antihistamines, or other sedatives [see
Warnings and Precautions (5.1)].
17.3
Carisoprodol Should Only Be Used for Short-Term Treatment
Patients should be advised that treatment with carisoprodol should be limited to acute use
(up to two or three weeks) for the relief of acute, musculoskeletal discomfort. In the
post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse
have been reported with prolonged use. If the musculoskeletal symptoms still persist,
patients should contact their healthcare provider for further evaluation.
1321 Pack Insert for Carisoprodol Tablets, USP 350 mg (Sciegen - Carlsbad) 450-11-15.indd 2
11/3/15 5:16 PM